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ASCO: Cancer, Obesity, and Diabetes

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Studies have suggested that obesity at diagnosis is linked to poor prognosis in certain cancers, though the link has not been well defined. In his opening speech at ASCO this year, the National Cancer Institute's Harold Varmus spoke of the link between obesity and cancer as one of the questions he would like researchers to tackle.

At a session on the topic of obesity and cancer risk, the German Cancer Research Center's Rudolf Kaaks spoke about studies he and others are conducting to determine if having a higher BMI poses an increased risk of cancer. Studies have shown that estrogen levels are high in adipose tissue, particularly in post-menopausal women, and the extra estrogen can add to a post-menopausal woman's risk of developing breast cancer. Hormones play an important role in tumor development, Kaaks added, and excess adiposity can lead to higher risk of cancer because of the added hormones that usually come along with a higher BMI. In addition, insulin resistance, also a feature of obesity or diabetes, is known to be a mechanism of tumor development, he added. Recent research has shown that the diabetes drug metformin, which lowers insulin levels, has been correlated with a decreased risk of various cancers.

In a separate session, the University of Toronto's Lorraine Lipscombe expanded on the work being done on the link between diabetes and cancer. The association between the two diseases was recognized as early as 1932, but it wasn't until very recently that it has begun to be extensively studied, Lipscombe said. The link is largely limited to type II diabetes, and has its strongest associations with pancreatic, liver, and endometrial cancers, though it has also been linked to breast, prostate, and colorectal cancers. Diabetes is in general is considered a marker of poor prognosis, Lipscombe said. Differences in healthc are given to cancer patients who have diabetes versus those who don't may also play a role in this association, as patients who have diabetes often receive less aggressive chemotherapy than those who don't. And diabetes itself may be to blame for lower survival rates in some cancers, particularly breast cancer, so the association between the two diseases, while there, needs more study, Lipscombe added. One possible mechanism is that glucose acts as a fuel for tumors, and, relatedly, insulin resistance, which leads to hyperinsulinemia and inflammation, may also be to blame in promoting cancer. A 2005 study showed that cancer mortality increased with higher fasting glucose levels in patients, and recent studies have shown that cancer risk increases even before diabetes develops, as pre-diabetic states cause higher insulin levels in patients, Lipscombe said. The link between insulin and cancer risk is particularly strengthened by studies that show that women with hormonal imbalances like polycystic ovarian syndrome, which has insulin resistance as a hallmark, also have an increased risk of certain cancers.

Because this link between the two diseases is becoming more prevalent, researchers are looking at new ways to treat both diseases together. Lipscombe's colleague Pamela Goodwin presented clinical data on the use of diabetes drug metformin in the treatment of cancer. Pre-clinical trials in mice have shown that metformin does have an effect on tumor growth. A recent meta-analysis of clinical studies of metformin shows it reduces cancer risk or mortality 30 percent when used to treat diabetes, mostly in pancreatic, breast, colorectal, and hepatocellular cancers, but also in lung cancer, Goodwin said. Both randomized and observational studies have shown that patients receiving metformin respond better to chemotherapy than those not receiving it. Insulin binds to breast cancer cells and stimulates cell growth, so metformin acts on the host as well as the cancer cells, by reducing insulin growth, and therefore taking away one of the tumor's mechanisms for growth, Goodwin added. In a study of non-diabetic women with breast cancer given metformin pre-surgery, researchers saw enhanced apoptosis, and a reduction in the biomarkers of cancer proliferation, indicating that the drug could be used in the treatment of cancer even in non-diabetics, Goodwin said. And studies in this area are just getting started. A recent look at the NIH/NCI listings shows that more than 20 studies are currently being conducted on metformin in various cancers, and the effects of the drug on inflammation, cancer stem cells, and in combination therapy.

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